Biosynthesis of Novel Ascorbic Acid Esters and Their Encapsulation in Lignin Nanoparticles as Carriers and Stabilizing Systems.

A dual-target strategy was designed for the application of lignin nanoparticles in the lipase mediated biosynthesis of novel 3-O-ethyl-L-ascorbyl-6-ferulate and 3-O-ethyl-L-ascorbyl-6-palmitate and in their successive solvent-shift encapsulation in order to improve stability and antioxidant activity against temperature and pH-dependent degradation. The loaded lignin nanoparticles were fully characterized in terms of kinetic release, radical scavenging activity and stability under pH 3 and thermal stress (60 °C), showing improved antioxidant activity and high efficacy in the protection of ascorbic acid esters from degradation.

Molecular Dynamics Investigations of Human DNA-Topoisomerase I Interacting with Novel Dewar Valence Photo-Adducts: Insights into Inhibitory Activity.

Chronic exposure to ultraviolet (UV) radiation is known to induce the formation of DNA photo-adducts, including cyclobutane pyrimidine dimers (CPDs) and Dewar valence derivatives (DVs). While CPDs usually occur at higher frequency than DVs, recent studies have shown that the latter display superior selectivity and significant stability in interaction with the human DNA/topoisomerase 1 complex (TOP1). With the aim to deeply investigate the mechanism of interaction of DVs with TOP1, we report here four all-atom molecular dynamic simulations spanning one microsecond. These simulations are focused on the stability and conformational changes of two DNA/TOP1-DV complexes in solution, the data being compared with the biomimetic thymine dimer counterparts. Results from root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) analyses unequivocally confirmed increased stability of the DNA/TOP1-DV complexes throughout the simulation duration. Detailed interaction analyses, uncovering the presence of salt bridges, hydrogen bonds, water-mediated interactions, and hydrophobic interactions, as well as pinpointing the non-covalent interactions within the complexes, enabled the identification of specific TOP1 residues involved in the interactions over time and suggested a potential TOP1 inhibition mechanism in action.

First Evidence of Pheomelanin-UVA-Driven Synthesis of Pummerer's Ketones by Peroxidase-Mediated Oxidative Coupling of Substituted Phenols.

Photoexcitation of pheomelanin produces high-energy singlet oxygen and the superoxide anion, which are reactive species in damage of cellular targets. In principle, these species can be involved in processes of synthetic utility when adequate experimental conditions are defined. Here, we describe that pheomelanin performs as a selective UVA antenna for the horseradish peroxidase oxidative coupling of substituted phenols to biologically active Pummerer's ketones under 2-methyltetrahydrofuran/buffer biphasic conditions. In this system, singlet oxygen is scavenged by conversion of 2-methyltetrahydrofuran into the corresponding organic hydroperoxide, while the superoxide anion is dismutated into hydrogen peroxide. Both these intermediates are able to oxidize the active site of horseradish peroxidase triggering the oxidative coupling reaction. Trimer derivatives, produced by addition of phenoxy radicals on preformed Pummerer's ketones were also isolated, suggesting the possibility to further improve the structural complexity of the reaction products.

Lignin Nanoparticles Deliver Novel Thymine Biomimetic Photo-Adducts with Antimelanoma Activity.

We report here the synthesis of novel thymine biomimetic photo-adducts bearing an alkane spacer between nucleobases and characterized by antimelanoma activity against two mutated cancer cell lines overexpressing human Topoisomerase 1 (TOP1), namely SKMEL28 and RPMI7951. Among them, Dewar Valence photo-adducts showed a selectivity index higher than the corresponding pyrimidine-(6-4)-pyrimidone and cyclobutane counterpart and were characterized by the highest affinity towards TOP1/DNA complex as evaluated by molecular docking analysis. The antimelanoma activity of novel photo-adducts was retained after loading into UV photo-protective lignin nanoparticles as stabilizing agent and efficient drug delivery system. Overall, these results support a combined antimelanoma and UV sunscreen strategy involving the use of photo-protective lignin nanoparticles for the controlled release of thymine dimers on the skin followed by their sacrificial transformation into photo-adducts and successive inhibition of melanoma and alert of cellular UV machinery repair pathways.

Nano-Structured Lignin as Green Antioxidant and UV Shielding Ingredient for Sunscreen Applications.

Green, biocompatible, and biodegradable antioxidants represent a milestone in cosmetic and cosmeceutical applications. Lignin is the most abundant polyphenol in nature, recovered as a low-cost waste from the pulp and paper industry and biorefinery. This polymer is characterized by beneficial physical and chemical properties which are improved at the nanoscale level due to the emergence of antioxidant and UV shielding activities. Here we review the use of lignin nanoparticles in cosmetic and cosmeceutical applications, focusing on sunscreen and antiaging formulations. Advances in the technology for the preparation of lignin nanoparticles are described highlighting structure activity relationships.